Upper extremity FES systems have assisted hundreds of individuals with cervical-level (i.e. C3-C6) SCI to use their hands and increase their independence and quality of life. These systems have relied on muscle-based electrodes, especially for the functions of the hand. Peripheral nerve electrodes have been extensively tested in animals and demonstrated selective stimulation and safety. Peripheral nerve electrodes offer several potential advantages compared to muscle-based electrodes, including complete muscle recruitment, multiple functions from a single implant, mechanical isolation from the muscle, lower stimulation power requirements, and no activitydependent recruitment. The long-term goal of this work is to implement highly selective, extraneural cuff electrodes, specifically the flat interface nerve electrode (FINE) in several neuroprosthesis applications. This purpose of this proposal is to assess the feasibility of using the FINE in upper extremity applications. The key steps in assessing feasibility are to collect quantitative measures of the fascicular anatomy of the upper extremity nerves, to select optimal implant locations, to select optimal electrode designs, and to demonstration intraoperatively the selectivity of stimulation with these electrodes. The proposal consists of three specific aims. 1) Generate quantitative anatomical data of the human upper extremity nerves. There is extensive literature on the qualitative anatomy of the upper extremity nerves, but little quantitative data required to design electrode sizes and create computer simulations for prediction electrode performance. 2) Develop neurobiomechanical models of upper extremities. Once the quantitative anatomy is available, finite element method (FEM) models can predict recruitment with cuff electrode stimulation. This provides a tool to optimize the electrode design prior to patient implementation. 3) Demonstrate nerve cuff performance in intraoperative trials. Once an electrode is designed and tested via computer models, the only true test of its capabilities is by testing in humans. Previous studies have shown that intraoperative measures of stimulation selectivity are good predictors of chronic selectivity. Therefore, acute, intraoperative testing can demonstrate whether or not the peripheral nerve stimulation is appropriate for upper extremity neuroprostheses systems. At the completion of the proposed work, we expect to have all the necessary data to show that an all-nerve cuff system can be permanently implanted in a patient to restore upper extremity function in mid- to high-cervical level SCI patients. We expect this work will make a significant impact in upper extremity FES applications and pave the path to other applications, such as neural interfaces for amputee prosthetics. [unreadable] [unreadable] [unreadable]